The Transgenic Animal Core will provide two core services to the projects described in this proposal: 1. Transgenic Services. The transgenic unit will provide pronuclear microinjection of DNA constructs into fertilized mouse eggs leading to the development of gene modified mouse lines expressing modified genes and gene products to facilitate imaging analysis. 2. Germline Modification Services. This unit will provide gene targeting technology services. Gene targeted mouse lines via ES cell lines will be developed, leading to homozygous knock-in constructs human genes of interest in this animal models.